Division of Urology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
Prostate Cancer Prostatic Dis. 2012 Mar;15(1):28-35. doi: 10.1038/pcan.2011.53. Epub 2012 Jan 17.
Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC), but the mechanisms underlying this relationship remain to be fully elucidated. Oxidative stress (OS) is a key process in the development and progression of PC. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy humans, but at reduced levels in obese subjects. Moreover, case-control studies also document lower levels of serum adiponectin in PC patients compared with healthy individuals.
Human 22Rv1 and DU-145 PC cell lines were examined for the generation of OS and detoxification of reactive oxygen species after treatment with adiponectin. Normality was confirmed using the Shapiro-Wilk test and results were analyzed using a one-way analysis of variance.
We demonstrate that adiponectin increased cellular anti-oxidative defense mechanisms and inhibited OS in a significant and dose-dependent manner. We show that adiponectin treatment decreased the generation of superoxide anion in both cell lines, whereas the transcript levels of NADPH oxidase (NOX)2 and NOX4 increased. We also found indications of an overall anti-oxidative effect, as the total anti-oxidative potential, catalase activity and protein levels, and manganese superoxide dismutase protein levels increased significantly (P<0.05) in both cell lines after treatment with adiponectin.
Lower levels of adiponectin in obese individuals may result in higher levels of prostatic OS, which may explain the clinical association between obesity, hypoadiponectinemia and PC.
新出现的数据表明肥胖会增加侵袭性前列腺癌（PC）的风险，但这种关系的机制仍有待充分阐明。氧化应激（OS）是 PC 发展和进展的关键过程。脂联素是一种脂肪细胞特异性激素，在健康人群中循环水平相对较高，但在肥胖人群中水平降低。此外，病例对照研究还记录到 PC 患者的血清脂联素水平低于健康个体。
用脂联素处理人 22Rv1 和 DU-145 PC 细胞系，观察 OS 的产生和活性氧的解毒作用。使用 Shapiro-Wilk 检验确认正态性，使用单向方差分析分析结果。
我们证明脂联素以显著的剂量依赖性方式增加细胞抗氧化防御机制并抑制 OS。我们表明，脂联素处理降低了两种细胞系中超氧阴离子的产生，而 NADPH 氧化酶（NOX）2 和 NOX4 的转录水平增加。我们还发现了整体抗氧化作用的迹象，因为在脂联素处理后，两种细胞系中的总抗氧化潜力、过氧化氢酶活性和蛋白水平以及锰超氧化物歧化酶蛋白水平均显著增加（P<0.05）。
肥胖个体中脂联素水平较低可能导致前列腺 OS 水平升高，这可能解释了肥胖、低脂联素血症与 PC 之间的临床关联。
